2-AMINO-N-HETEROARYL-NICOTINAMIDES AS NAV1.8 INHIBITORS

1 . A compound of structural Formula I:

or a pharmaceutically acceptable salt thereof, wherein

A is heteroaryl or heteroaryl fused to a saturated or unsaturated 5- or 6-membered ring containing 0-3 heteroatoms independently selected from O, S and N(R h ) q , wherein each heteroaryl, 5-membered ring and 6-membered ring is unsubstituted or substituted with one to five substituents selected from R a ;

B is heteroaryl, wherein heteroaryl is unsubstituted or substituted with one to three substituents selected from R b ;

R 1 is selected from the group consisting of:

(1) hydrogen,

(2) —SO 3 H,

(3) —SO 2 NH 2 ,

(4) —SO 2 NR e C 1-6 alkyl,

(5) —SO 2 NR e C(O)C 1-6 alkyl,

(6) —SO 2 NR e C 2-6 alkenyl,

(7) —SO 2 NR e C 3-6 cycloalkyl,

(8) —SO 2 NR e C(O)C 3-6 cycloalkyl,

(9) —SO 2 NR e C 2-6 cycloheteroalkyl,

(10) —SO 2 NR e C(O)C 2-6 cycloheteroalkyl,

(11) —SO 2 NR e -aryl,

(12) —SO 2 NR e -heteroaryl,

(13) —SO 2 C 1-6 alkyl,

(14) —SO 2 C 1-6 alkenyl,

(15) —SO 2 C 3-6 cycloalkyl,

(16) —SO 2 C 2-6 cycloheteroalkyl,

(17) —SO 2 aryl,

(18) —SO 2 heteroaryl,

(19) —S(O)R j ,

(20) —SR j ,

(21) —C(O)NH 2 ,

(22) —C(O)NR e R j ,

(23) —CO 2 H,

(24) —CO 2 R j ,

(25) —C(O)R j ,

(26) —CN,

(27) CF 3 ,

(28) halogen,

(29) —OH,

(30) —OC 1-6 alkyl,

(31) —OC 2-6 alkenyl,

(32) —OC 3-6 cycloalkyl,

(33) —OC 2-6 cycloheteroalkyl,

(34) —O-aryl,

(35) —O-heteroaryl,

(36) —OC(O)R j ,

(37) —OC(O)NR e R j ,

(38) —OC(O)N(R j ) 2 ,

(39) —C 1-6 alkyl,

(40) —C 2-6 alkenyl,

(41) —C 1-6 cycloalkyl,

(42) —C 2-6 cycloheteroalkyl,

(43) aryl,

(44) heteroaryl,

(45) —(CH 2 ) n NR e C(O)R j ,

(46) —(CH 2 ) n NR e C(O)OR j ,

(47) —(CH 2 ) n NR e C(O)N(R e ) 2 ,

(48) —(CH 2 ) n NR e C(O)NR e R j ,

(49) —(CH 2 ) n NR e C(O)N(R j ) 2 ,

(50) —(CH 2 ) n NR e S(O) m R j ,

(51) —(CH 2 ) n NR e S(O) m N(R e ) 2 ,

(52) —(CH 2 ) n NR e S(O) m NR e R j ,

(53) —(CH 2 ) n NR e S(O) m N(R j ) 2 , and

(54) —(CH 2 ) n NR e R j ,

wherein each CH 2 , alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to four substituents selected from R d ;

R 2 is selected from the group consisting of:

(1) hydrogen, and

(2) —C 1-6 alkyl;

R 3 is selected from the group consisting of:

(1) a monocyclic, bicyclic or spirocyclic C 3-12 cycloalkyl ring, and

(2) a monocyclic, bicyclic or spirocyclic C 2-12 cycloheteroalkyl ring,

wherein the cycloheteroalkyl contains 1-4 heteroatoms independently selected from N(R m ) r , O, and S, wherein each cycloalkyl ring and each cycloheteroalkyl ring may be fused to an aryl or heteroaryl, and wherein each cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to eight substitutents selected from R c ;

each R a is selected from the group consisting of:

(1) —C 1-6 alkyl,

(2) —OC 1-6 alkyl,

(3) halogen,

(4) —OH,

(5) oxo,

(6) —CN,

(7) —C 3-6 cycloalkyl, and

(8) —C 2-5 cycloheteroalkyl,

wherein each alkyl, cycloalkyl and cycloheteroalkyl is unsubstituted or substituted with one to six substituents selected from halogen, OH, NH 2 , NH(C 1-6 alkyl) and N(C 1-6 alkyl) 2 ;

each R b is independently selected from the group consisting of:

(1) —CF 3 ,

(2) —CF 2 CF 3

(3) —CHF 2 ,

(4) —OCHF 2 ,

(5) —OCH 2 CF 3 ,

(6) —OCF 3 ,

(7) CN,

(8) halogen,

(9) —Si(C 1-6 alkyl) 3 ,

(10) —C 1-6 alkyl-O—R k ,

(11) —C 1-6 alkyl,

(12) —C 2-6 alkenyl,

(13) —C 2-6 alkynyl,

(14) —C 3-6 cycloalkyl,

(15) —C 2-6 cycloheteroalkyl,

(16) aryl,

(17) heteroaryl,

(18) —C 1-6 alkyl-C 3-6 cycloalkyl,

(19) —C 1-6 alkyl-C 2-6 cycloheteroalkyl,

(20) —C 1-6 alkyl-aryl,

(21) —C 1-6 alkyl-heteroaryl,

(22) —C 2-6 alkenyl-C 3-6 cycloalkyl,

(23) —C 2-6 alkenyl-C 2-6 cycloheteroalkyl,

(24) —C 2-6 alkenyl-aryl,

(25) —C 2-6 alkenyl-heteroaryl,

(26) —C 2-6 alkynyl-C 3-6 cycloalkyl,

(27) —C 2-6 alkynyl cycloheteroalkyl,

(28) —C 2-6 alkynyl-aryl,

(29) —C 2-6 alkynyl-heteroaryl,

(30) NO 2 ,

(31) —OH,

(32) —(CH 2 ) p —OC 1-6 alkyl,

(33) —(CH 2 ) p —OC 2-6 alkenyl,

(34) —(CH 2 ) p —OC 2-6 alkynyl,

(35) —(CH 2 ) p —OC 3-6 cycloalkyl,

(36) —(CH 2 ) p —OC 2-6 heterocycloalkyl,

(37) —(CH 2 ) p —O-aryl,

(38) —(CH 2 ) p —O-heteroaryl,

(39) —OC 1-6 alkyl-C 3-6 cycloalkyl,

(40) —OC 1-6 alkyl-C 2-6 heterocycloalkyl,

(41) —OC 1-6 alkyl-aryl,

(42) —OC 1-6 alkyl-heteroaryl,

(1) —S(O) m R k ,

(43) —C 1-6 alkyl-S(O) m R k ,

(44) —C(O)R k ,

(45) —N(R i ) 2 , and

(46) —NR i R k ,

wherein each R b is unsubstituted or substituted with one to five substituents selected from R f ;

each R c is independently selected from the group consisting of:

(1) —CF 3 ,

(2) —CH 2 CF 3 ,

(3) —CHF 2 ,

(4) —OCHF 2 ,

(5) —OCF 3 ,

(6) CN,

(7) oxo,

(8) —OH,

(9) halogen,

(10) —C 1-6 alkyl,

(11) —C 2-6 alkenyl,

(12) —C 2-6 alkynyl,

(13) —C 3-6 cycloalkyl,

(14) —C 2-6 cycloheteroalkyl,

(15) —C 1-6 alkyl-C 3-6 cycloalkyl,

(16) —C 1-6 alkyl-C 2-6 cycloheteroalkyl,

(17) —C 1-6 alkyl-aryl,

(18) —C 1-6 alkyl-heteroaryl,

(19) —C 1-6 alkenyl-C 3-6 cycloalkyl,

(20) —C 1-6 alkenyl-aryl,

(21) —C 1-6 alkenyl heteroaryl,

(22) —C 1-6 alkenyl-C 2-6 cycloheteroalkyl,

(23) —C 2-6 alkynyl-C 3-6 cycloalkyl,

(24) —C 2-6 alkynyl-C 2-6 cycloheteroalkyl,

(25) —C 2-6 alkynyl-aryl,

(26) —C 2-6 alkynyl heteroaryl,

(27) —OC 1-6 alkyl,

(28) —OC 2-6 alkenyl,

(29) —OC 2-6 alkynyl,

(30) —OC 3-6 cycloalkyl,

(31) —OC 2-6 heterocycloalkyl,

(32) —O-aryl,

(33) —O-heteroaryl,

(34) —OC 1-6 alkyl-cycloalkyl,

(35) —OC 1-6 alkyl-cycloheteroalkyl,

(36) —OC 1-6 alkyl-aryl,

(37) —OC 1-6 alkyl-heteroaryl,

(38) —S(O) m R L ,

(39) —S(O)R L ,

(40) —S—R L ,

(41) —C 1-6 alkyl-S(O) m R L ,

(42) —C(O)R L ,

(43) —C(O)C 1-6 alkyl-R L ,

(44) —OC(O)R L ,

(45) —CO 2 R L ,

(46) aryl, and

(47) heteroaryl,

wherein each R c is unsubstituted or substituted with one to five substituents selected from R g ;

R d is independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) OH,

(4) oxo,

(5) —C 1-6 alkyl,

(6) —OC 1-6 alkyl,

(7) NH 2 ,

(8) NH(C 1-6 alkyl), and

(9) N(C 1-6 alkyl) 2 ;

each R e is independently selected from the group consisting of:

(1) hydrogen, and

(2) —C 1-6 alkyl;

each R f is selected from the group consisting of:

(1) halogen, F

(2) —C 1-6 alkyl,

(3) —OH,

(4) —OC 1-6 alkyl,

(5) —OC 3-6 cycloalkyl,

(6) —OC 2-6 cycloheteroalkyl,

(7) CN,

(8) —NH 2 ,

(9) —NH(C 1-6 alkyl),

(10) —NH(C 3-6 cycloalkyl),

(11) —NH(C 2-6 cycloheteroalkyl),

(12) —N(C 1-6 alkyl) 2 ,

(13) —N(C 3-6 cycloalkyl) 2 , and

(14) —N(C 2-6 cycloheteroalkyl) 2 ,

wherein each alkyl, cycloalkyl, and cycloheteroalkyl is unsubstituted or substituted with one to three substituents independently selected from: —OH, halogen, cyano, and —S(O) 2 CH 3 ;

each R g is selected from the group consisting of:

(1) halogen,

(2) C 1-6 alkyl,

(3) —OH,

(4) —OC 1-6 alkyl,

(5) —S(O) m —C 1-6 alkyl,

(6) —CN,

(7) —CF 3 ,

(8) —OCHF 2 , and

(9) —OCF 3 ,

wherein each alkyl is unsubstituted or substituted with one to three substituents independently selected from: —OH, halogen, cyano, and —S(O) 2 CH 3 ;

each R h is independently selected from the group consisting of:

(1) hydrogen, and

(2) —C 1-6 alkyl;

each R i is independently selected from the group consisting of:

(1) hydrogen, and

(2) —C 1-6 alkyl;

each R j is selected from the group consisting of:

(1) —C 1-6 alkyl,

(2) —C 2-6 alkenyl,

(3) —C 3-6 cycloalkyl,

(4) —C 2-6 cycloheteroalkyl,

(5) aryl, and

(6) heteroaryl,

wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three substituents independently selected from: —C 1-6 alkyl, —C 3-6 cycloalkyl, —OH, —OC 1-6 alkyl, —OC 3-6 cycloalkyl, halogen, cyano, and —S(O) 2 CH 3 ;

each R k is selected from the group consisting of:

(1) —C 1-6 alkyl,

(2) —C 2-6 alkenyl,

(3) —C 3-6 cycloalkyl,

(4) —C 3-6 cycloalkyl,

(5) —C 2-6 cycloheteroalkyl,

(6) aryl, and

(7) heteroaryl,

wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three substituents independently selected from: —C 1-6 alkyl, —C 3-6 cycloalkyl, —OH, —OC 1-6 alkyl, —OC 3-6 cycloalkyl, halogen, cyano, and —S(O) 2 CH 3 ;

each R L is selected from the group consisting of:

(1) —C 1-6 alkyl,

(2) —C 2-6 alkenyl,

(3) —C 3-6 cycloalkyl,

(4) —C 2-6 cycloheteroalkyl,

(5) aryl, and

(6) heteroaryl,

wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three substituents independently selected from: —C 1-6 alkyl, —C 3-6 cycloalkyl, —OH, —OC 1-6 alkyl, —OC 3-6 cycloalkyl, halogen, cyano, and —S(O) 2 CH 3 ;

each R m is independently selected from the group consisting of:

(1) hydrogen, and

(2) —C 1-6 alkyl;

each n is independently 0, 1, 2, 3 or 4;

each m is independently 0, 1 or 2;

each p is independently 0, 1, 2, 3 or 4;

each q is independently 0 or 1; and

each r is independently 0 or 1.

2 . The compound according to claim 1 wherein R 2 is hydrogen; or a pharmaceutically acceptable salt thereof.

3 . The compound according to claim 1 wherein A is heteroaryl, wherein heteroaryl is unsubstituted or substituted with one to four substituents selected from R a ; or a pharmaceutically acceptable salt thereof.

4 . The compound according to claim 1 wherein A is selected from the group consisting of:

(1) pyridine,

(2) pyrimidine,

(3) pyrazine,

(4) indazole,

(5) imidazo[1,2-a]pyridine,

(6) pyrrolo[3,2-c]pyridine,

(7) pyrrolo[2,3-b]pyridine,

(8) pyrazole,

(9) thiophene, and

(10) 1,2,4-oxadiazole,

wherein A is unsubstituted or substituted with one to four substituents selected from R a ; or a pharmaceutically acceptable salt thereof.

5 . The compound according to claim 1 wherein A is pyridine, wherein pyridine is unsubstituted or substituted with one to three substituents selected from R a ; or a pharmaceutically acceptable salt thereof.

6 . The compound according to claim 1 wherein B is selected from the group consisting of:

(1) pyrazine,

(2) pyridine,

(3) pyrimidine, and

(4) pyridazine,

wherein each B is unsubstituted or substituted with one to three substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

7 . The compound according to claim 1 wherein B is selected from the group consisting of:

(1) pyridine,

(2) pyrimidine, and

(3) pyridazine,

wherein each B is unsubstituted or substituted with one to three substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

8 . The compound according to claim 1 wherein B is pyridine, wherein pyridine is unsubstituted or substituted with one to three substituents selected from R b ; or a pharmaceutically acceptable salt thereof.

9 . The compound according to claim 1 wherein R 1 is selected from the group consisting of:

(1) —SO 2 NH 2 ,

(2) —SO 2 C 1-6 alkyl,

(3) —SO 2 NH—C 1-6 alkyl,

(4) —SO 2 C 3-6 cycloalkyl,

(5) —C(O)NH 2 ,

(6) —CO 2 H,

(7) —CN,

(8) halogen,

(9) —OH,

(10) —OC 1-6 alkyl,

(11) —C 1-6 alkyl, and

(12) —CF 3 ,

wherein each alkyl, and cycloalkyl is unsubstituted or substituted with one to three substituents selected from R d ; or a pharmaceutically acceptable salt thereof.

10 . The compound according to claim 1 wherein R 1 is selected from the group consisting of:

(1) —SO 2 NH 2 ,

(2) —C(O)NH 2 , and

(3) —OH;

or a pharmaceutically acceptable salt thereof.

11 . The compound according to claim 1 wherein R 3 is selected from the group consisting of: a monocyclic, bicyclic or spirocyclic C 3-8 cycloalkyl ring, and a monocyclic, bicyclic or spirocyclic C 2-12 cycloheteroalkyl ring, wherein the cycloheteroalkyl contains 1-4 heteroatoms independently selected from N(R m ) r , O, and S, and wherein each cycloalkyl and cycloheteroalkyl is unsubstituted or substituted with one to eight substitutents selected from R c ; or a pharmaceutically acceptable salt thereof.

12 . The compound according to claim 1 wherein R 3 is a monocyclic, bicyclic or spirocyclic C 2-12 cycloheteroalkyl ring, wherein the cycloheteroalkyl contains a nitrogen and 0-3 heteroatoms independently selected from N(R m ) r , O, and S, and wherein each cycloheteroalkyl is unsubstituted or substituted with one to eight substitutents selected from R c ; or a pharmaceutically acceptable salt thereof.

13 . The compound according to claim 1 wherein R 3 is selected from the group consisting of:

(1) cyclohexane,

(2) cycloheptane,

(3) pyrrolidine,

(4) azetidine,

(5) piperidine,

(6) piperazine,

(7) azepane,

(8) morpholine,

(9) thiomorpholine,

(10) oxazepane,

(11) isoindoline,

(12) dihydroisoquinoline,

(13) azabicyclo[2.2.1]heptane,

(14) azabicyclo[3.1.1]heptane,

(15) azabicyclo[4.1.0]heptane,

(16) azabicyclo[3.2.1]octane,

(17) azabicyclo[3.2.0]heptane,

(18) azaspiro[2.5]octane,

(19) dihydrothieno[3,2-c]pyridine,

(20) dihydroimidazo[1,2-a]pyrazine, and

(21) hexahydrofuro[3,2-b]pyrrole,

wherein R 3 is unsubstituted or substituted with one to eight substituents selected from R c ; or a pharmaceutically acceptable salt thereof.

14 . The compound according to claim 1 wherein R 3 is selected from the group consisting of:

(1) pyrrolidine,

(2) azetidine,

(3) piperidine,

(4) piperazine,

(5) azepane,

(6) morpholine,

(7) thiomorpholine,

(8) oxazepane,

(9) isoindoline,

(10) dihydroisoquinoline,

(11) azabicyclo[2.2.1]heptane,

(12) azabicyclo[3.1.1]heptane,

(13) azabicyclo[4.1.0]heptane,

(14) azabicyclo[3.2.1]octane,

(15) azabicyclo[3.2.0]heptane,

(16) azaspiro[2.5]octane,

(17) dihydrothieno[3,2-c]pyridine,

(18) dihydroimidazo[1,2-a]pyrazine, and

(19) hexahydrofuro[3,2-b]pyrrole,

wherein R 3 is unsubstituted or substituted with one to eight substituents selected from R c ;

or a pharmaceutically acceptable salt thereof.

15 . The compound according to claim 1 wherein R 3 is selected from the group consisting of:

(1) piperidine,

(2) azepane, and

(3) morpholine,

wherein R 3 is unsubstituted or substituted with one to six substituents selected from R c ; or a pharmaceutically acceptable salt thereof.

16 . The compound according to claim 1 wherein

A is selected from the group consisting of:

(1) pyridine,

(2) pyrimidine,

(3) pyrazine,

(4) indazole,

(5) imidazo[1,2-a]pyridine,

(6) pyrrolo[3,2-c]pyridine,

(7) pyrrolo[2,3-b]pyridine,

(8) pyrazole,

(9) thiophene, and

(10) 1,2,4-oxadiazole,

wherein A is unsubstituted or substituted with one to four substituents selected from R a ;

B is selected from the group consisting of:

(1) pyridine,

(2) pyrimidine, and

(3) pyridazine,

wherein each B is unsubstituted or substituted with one to four substituents selected from R b ;

R 1 is selected from the group consisting of:

(1) —SO 3 H,

(2) —SO 2 NH 2 ,

(3) —SO 2 C 1-6 alkyl,

(4) —SO 2 NH—C 1-6 alkyl,

(5) —SO 2 C 3-6 cycloalkyl,

(6) —C(O)NH 2 ,

(7) —CO 2 H,

(8) —CN,

(9) halogen,

(10) —OH,

(11) —OC 1-6 alkyl,

(12) —C 1-6 alkyl, and

(13) —CF 3 ,

wherein each alkyl, and cycloalkyl is unsubstituted or substituted with one to three substituents selected from R d ;

R 2 is hydrogen;

R 3 is selected from the group consisting of:

(1) pyrrolidine,

(2) azetidine,

(3) piperidine,

(4) piperazine,

(5) azepane,

(6) morpholine,

(7) thiomorpholine,

(8) oxazepane,

(9) isoindoline,

(10) dihydroisoquinoline,

(11) azabicyclo[2.2.1]heptane,

(12) azabicyclo[3.1.1]heptane,

(13) azabicyclo[4.1.0]heptane,

(14) azabicyclo[3.2.1]octane,

(15) azabicyclo[3.2.0]heptane,

(16) azaspiro[2.5]octane,

(17) dihydrothieno[3,2-c]pyridine,

(18) dihydroimidazo[1,2-a]pyrazine, and

(19) hexahydrofuro[3,2-b]pyrrole,

wherein R 3 is unsubstituted or substituted with one to eight substituents selected from R c ; or a pharmaceutically acceptable salt thereof.

17 . The compound according to claim 1 wherein

A is pyridine, wherein pyridine is unsubstituted or substituted with one to three substituents selected from R a ;

B is pyridine, wherein pyridine is unsubstituted or substituted with one to three substituents selected from R b ;

R 1 is selected from the group consisting of:

(1) —SO 2 NH 2 ,

(2) —C(O)NH 2 , and

(3) —OH;

R 2 is hydrogen;

R 3 is selected from the group consisting of:

(1) piperidine,

(2) azepane, and

(3) morpholine,

wherein R 3 is unsubstituted or substituted with one to six substituents selected from R c ; or a pharmaceutically acceptable salt thereof.

18 . The compound according to claim 1 selected from:

1) 2-(4,4-difluoropiperidin-1-yl)-N-(6-sulfamoylpyrazin-2-yl)-5-(trifluoromethyl)-nicotinamide;

2) 2-(4,4-difluoropiperidin-1-yl)-N-(4-hydroxypyrimidin-2-yl)-5-(trifluoromethyl)-nicotinamide;

3) 5-(2-(4,4-difluoropiperidin-1-yl)-5-(trifluoromethyl)nicotinamido)picolinic acid;

4) 4-(2-(4,4-difluoropiperidin-1-yl)-5-(trifluoromethyl)nicotinamido)picolinic acid;

5) N-(6-cyanopyridin-3-yl)-2-(4,4-difluoropiperidin-1-yl)-5-(trifluoromethyl)nicotinamide;

6) 2-(azepan-1-yl)-N-(5-(methylsulfonyl)pyridin-3-yl)-5-(trifluoromethyl)nicotinamide;

7) 2-(3-(hydroxymethyl)piperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

8) 2-(azepan-1-yl)-N-(5-carbamoylpyridin-3-yl)-5-(trifluoromethyl)nicotinamide;

9) 2-(4,4-difluoro-1-piperidyl)-6-methyl-N-(5-sulfamoyl-3-pyridyl)pyridine-3-carboxamide;

10) 5-chloro-2-(4,4-difluoro-1-piperidyl)-N-(5-sulfamoyl-3-pyridyl)pyridine-3-carboxamide;

11) 6-chloro-2-(4,4-difluoropiperidin-1-yl)-4-methyl-N-(5-sulfamoylpyridin-3-yl)nicotinamide;

12) 5,6-dicyclopropyl-2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

13) 2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

14) 5-cyclopropyl-2-(4,4-difluoropiperidin-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

15) 5-cyclobutyl-2-(4,4-difluoropiperidin-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

16) 5-(cyclopropylethynyl)-2-(4,4-difluoropiperidin-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

17) 2-(4,4-difluoroazepan-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

18) 6-(cyclopropylmethyl)-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

19) 2-(4,4-difluoroazepan-1-yl)-5,6-dimethyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

20) 5-cyclopropyl-2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(2,2,2-trifluoroethoxy)nicotinamide;

21) 5-chloro-6-cyclopropyl-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-nicotinamide;

22) 6-cyclopropyl-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

23) 5-chloro-6-cyclobutyl-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-nicotinamide;

24) 6-cyclobutyl-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

25) 2-(5,5-Difluoro-2-oxoazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

26) 2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

27) 5-chloro-6-cyclopropyl-2-(4,4-difluoroazepan-1-yl)-N-(2-oxo-1,2-dihydropyridin-4-yl)-nicotinamide;

28) 2-(5,5-Difluoro-2-oxoazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

29) 2-(4,4-Dichloropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

30) 2-(4,4-difluoroazepan-1-yl)-N-[1-(methylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-5-(trifluoromethyl)pyridine-3-carboxamide;

31) 5-chloro-2-(4,4-difluoroazepan-1-yl)-6-methyl-N-[1-(methylsulfonyl)-1H-pyrazol-4-yl]pyridine-3-carboxamide;

32) 5-chloro-2-(4,4-difluoroazepan-1-yl)-4,6-dimethyl-N-[1-(methylsulfonyl)-1H-pyrazol-4-yl]pyridine-3-carboxamide;

33) N-{1-[(2-aminoethyl)sulfonyl]-1H-pyrazol-4-yl}-5-chloro-2-(4,4-difluoroazepan-1-yl)-6-methylpyridine-3-carboxamide;

34) 2-(4,4-difluoroazepan-1-yl)-N-[1-(methylsulfonyl)-1H-indazol-3-yl]-5-(trifluoromethyl)-pyridine-3-carboxamide;

35) 2-(4,4-difluoroazepan-1-yl)-N-[1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]-5-(trifluoromethyl)pyridine-3-carboxamide;

36) N-[1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl]-2-(4,4-difluoroazepan-1-yl)-5-(trifluoro-methyl)pyridine-3-carboxamide;

37) N-[5-cyclopropyl-1-(methylsulfonyl)-1H-pyrazol-4-yl]-2-(4,4-difluoroazepan-1-yl)-5-(trifluoromethyl)pyridine-3-carboxamide;

38) 2-cyclopropyl-4-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)pyrimidine-5-carboxamide;

39) 6-cyclopropyl-3-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)pyridazine-4-carboxamide;

40) 6-methyl-N-(2-sulfamoylpyridin-4-yl)-2-(3,4,4-trifluoroazepan-1-yl)nicotinamide;

41) 5-chloro-2-(4,4-difluoroazepan-1-yl)-6-methoxy-N-(2-sulfamoylpyridin-4-yl)pyridine-3-carboxamide;

42) N-[2-(tert-butylsulfamoyl)pyridin-4-yl]-5-chloro-2-(4,4-difluoroazepan-1-yl)-6-methoxy-pyridine-3-carboxamide;

43) 5-cyano-2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoromethyl)-nicotinamide;

44) 5-(cyclopropylethynyl)-2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoromethyl)nicotinamide;

45) 2-(azepan-1-yl)-N-(3-cyano-1,2,4-oxadiazol-5-yl)-5-(trifluoromethyl)pyridine-3-carboxamide;

46) 5-(cyclopropylmethyl)-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

47) (S)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoro-methyl)nicotinamide;

48) (R)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoro-methyl)-nicotinamide;

49) (R)-2-(4,4-dichloro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoro-methyl)nicotinamide;

50) (S)-2-(4,4-dichloro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoro-methyl)nicotinamide;

51) 2-(4,4-Dichloroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

52) 2-[(3S,5R)-4,4-difluoro-3,5-dimethyl-1-piperidyl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

53) 5-chloro-2-[(3S,5R)-4,4-difluoro-3,5-dimethyl-1-piperidyl]-6-methyl-N-(2-sulfamoyl-4-pyridyl)pyridine-3-carboxamide;

54) (S)-5-chloro-2-(4,4-difluoro-3-methylpiperidin-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

55) (R)-5-chloro-2-(4,4-difluoro-3-methylpiperidin-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

56) (S)-2-(3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

57) (R)-2-(3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

58) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[(1S,5S)-1-(trifluoromethyl)-3-azabicyclo[3.2.0]heptan-3-yl]pyridine-3-carboxamide;

59) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[(1R,5R)-1-(trifluoromethyl)-3-azabicyclo[3.2.0]heptan-3-yl]pyridine-3-carboxamide;

60) N-(2-sulfamoylpyridin-4-yl)-2-((1R,5S)-6,6,7,7-tetrafluoro-3-azabicyclo[3.2.0]heptan-3-yl)-5-(trifluoromethyl)nicotinamide;

61) 2-[(1S,6S)-7,7-difluoro-6-methyl-3-azabicyclo[4.1.0]heptan-3-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

62) 2-[(1R,6R)-7,7-difluoro-6-methyl-3-azabicyclo[4.1.0]heptan-3-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

63) 2-((1R,5S)-8,8-difluoro-3-oxaoctan-3-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

64) 2-((1R,5S)-6,6-difluoro-3-azabicyclo[3.2.0]heptan-3-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

65) 2-((1S,5R)-6,6-difluoro-3-azabicyclo[3.2.0]heptan-3-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

66) (R)-2-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

67) (S)-2-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

68) 2-((1R,5S)-3-azabicyclo[3.2.0]heptan-3-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

69) 2-((l S,6S)-7,7-difluoro-3-azabicyclo[4.1.0]heptan-3-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

70) 2-((1R,6R)-7,7-difluoro-3-azabicyclo[4.1.0]heptan-3-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

71) 2-[(1R,4R)-5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

72) 2-[(1S,4S)-5,5-difluoro-2-azabicyclo[2.2.1]heptan-2-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

73) (R)-2-(4,4-difluoro-2-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

74) (S)-2-(4,4-difluoro-2-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

75) 2-((3R,4s,5S)-4-hydroxy-3,4,5-trimethylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

76) 2-((1R,5S)-6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

77) 2-[(3S,4S)-4-hydroxy-3-methyl-1-piperidyl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-pyridine-3-carboxamide;

78) 2-[(3S,4r,5R)-4-hydroxy-3,5-dimethyl-1-piperidyl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoro-methyl)pyridine-3-carboxamide;

79) 2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoro-methyl)pyridine-3-carboxamide;

80) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[3-(trifluoromethyl)-1-piperidyl]pyridine-3-carboxamide;

81) 2-[3-(3,5-difluorophenyl)-1-piperidyl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-pyridine-3-carboxamide;

82) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[4-(trifluoromethyl)-1-piperidyl]pyridine-3-carboxamide;

83) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[3-[[4-(trifluoromethyl)phenyl]methyl]-1-piperidyl]pyridine-3-carboxamide;

84) N-(2-sulfamoyl-4-pyridyl)-2-thiomorpholino-5-(trifluoromethyl)pyridine-3-carboxamide;

85) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl]pyridine-3-carboxamide;

86) 2-(3-benzyl-6,8-dihydro-5H-imidazo[1,2-a]pyrazin-7-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

87) 2-[3,3-dimethyl-4-(2,2,2-trifluoroethyl)piperazin-1-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

88) 2-(2,2-dimethylmorpholin-4-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

89) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[8-(trifluoromethyl)-3,4-dihydro-1H-isoquinolin-2-yl]pyridine-3-carboxamide;

90) N-(2-sulfamoyl-4-pyridyl)-2-[4-(trifluoromethoxy)isoindolin-2-yl]-5-(trifluoromethyl)-pyridine-3-carboxamide;

91) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[2-[4-(trifluoromethyl)phenyl]morpholin-4-yl]pyridine-3-carboxamide;

92) N-(2-sulfamoyl-4-pyridyl)-2-(3,3,4,4-tetrafluoropyrrolidin-1-yl)-5-(trifluoromethyl)-pyridine-3-carboxamide;

93) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[3-(trifluoromethyl)azetidin-1-yl]pyridine-3-carboxamide;

94) 2-(3-pyrazol-1-ylpyrrolidin-1-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

95) 2-[2-(4-fluorophenyl)-1-piperidyl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

96) 2-(2,3,3a,5,6,6a-hexahydrofuro[3,2-b]pyrrol-4-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoro-methyl)pyridine-3-carboxamide;

97) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[3-[4-(trifluoromethyl)phenoxy]azetidin-1-yl]pyridine-3-carboxamide;

98) N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-2-[4-[3-(trifluoromethyl)phenoxy]-1-piperidyl]pyridine-3-carboxamide;

99) 2-[4-(cyclopropylmethyl)-3-oxo-piperazin-1-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoro-methyl)pyridine-3-carboxamide;

100) N-(2-sulfamoyl-4-pyridyl)-2-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]-5-(trifluoromethyl)-pyridine-3-carboxamide;

101) 5-chloro-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoyl-4-pyridyl)pyridine-3-carboxamide;

102) 2-((2R,6S)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

103) 2-((2S,6R)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

104) (S)—N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-2-(2-(trifluoromethyl)-1,4-oxazepan-4-yl)nicotinamide;

105) (R)—N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-2-(2-(trifluoromethyl)-1,4-oxazepan-4-yl)nicotinamide;

106) 2-[(2R)-6,6-dimethyl-2-(trifluoromethyl)-1,4-oxazepan-4-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

107) 2-(2,2-dimethyl-1,4-oxazepan-4-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

108) 2-[(7S)-7-methyl-1,4-oxazepan-4-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-pyridine-3-carboxamide;

109) N-[2-(tert-butylsulfamoyl)-4-pyridyl]-5-chloro-2-(4,4-difluoroazepan-1-yl)pyridine-3-carboxamide;

110) 2-[(2S)-2-methylmorpholin-4-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

111) 2-[(2R)-2-methyl-1,4-oxazepan-4-yl]-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-pyridine-3-carboxamide;

112) 2-(3-hydroxy-3-methyl-1-piperidyl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

113) 2-(6-fluoro-1,1-dimethyl-isoindolin-2-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)-pyridine-3-carboxamide;

114) 2-(azepan-1-yl)-N-(2-methyl-5-sulfamoylthiophen-3-yl)-5-(trifluoromethyl)pyridine-3-carboxamide;

115) 2-(4,4-difluoro-5-methylazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-pyridine-3-carboxamide;

116) 5-chloro-2-[(7R)-7-(difluoromethyl)-1,4-oxazepan-4-yl]-6-methyl-N-(2-sulfamoylpyridin-4-yl)pyridine-3-carboxamide;

117) 5-chloro-2-[(7S)-7-(difluoromethyl)-1,4-oxazepan-4-yl]-6-methyl-N-(2-sulfamoylpyridin-4-yl)pyridine-3-carboxamide;

118) (R)—N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-2-(7-(trifluoromethyl)-1,4-oxazepan-4-yl)nicotinamide;

119) (S)—N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-2-(7-(trifluoromethyl)-1,4-oxazepan-4-yl)nicotinamide;

120) 2-[(2S,7R)-2-methyl-7-(trifluoromethyl)-1,4-oxazepan-4-yl]-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)pyridine-3-carboxamide;

121) 2-((2R,7S)-2-methyl-7-(trifluoromethyl)-1,4-oxazepan-4-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

122) 2-((2R,7R)-2-methyl-7-(trifluoromethyl)-1,4-oxazepan-4-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

123) 2-((2S,7S)-2-methyl-7-(trifluoromethyl)-1,4-oxazepan-4-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

124) (S)-5-chloro-2-(2-(difluoromethyl)morpholino)-6-methyl-N-(2-sulfamoylpyridin-4-yl)-nicotinamide;

125) (R)-5-chloro-2-(2-(difluoromethyl)morpholino)-6-methyl-N-(2-sulfamoylpyridin-4-yl)-nicotinamide;

126) N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyridine-3-carboxamide;

127) (R)—N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-2-(2-(trifluoromethyl)pyrrolidin-1-yl)nicotinamide;

128) N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-2-[3-(trifluoromethyl)pyrrolidin-1-yl]pyridine-3-carboxamide;

129) (S)-2-(3-cyanopyrrolidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

130) (R)-2-(3-cyanopyrrolidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl-)nicotinamide;

131) 2-(4,4-difluoro-3-methylazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

132) 2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoromethyl)nicotinamide;

133) 2-((2R,6S)-2-ethyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

134) 2-((2S,6R)-2-ethyl-6-(trifluoromethyl)-morpholino)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

135) (R)-2-(2,2-dimethyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

136) (S)-2-(2,2-dimethyl-6-(trifluoromethyl)-morpholino)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

137) 4-(2-(4,4-difluoroazepan-1-yl)-5-(trifluoromethyl)nicotinamido)picolinamide;

138) 6-chloro-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoyl-4-pyridyl)pyridine-3-carboxamide;

139) 2-(azepan-1-yl)-N-(2-sulfamoyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

140) 2-(azepan-1-yl)-N-(2-methylsulfonyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

141) 2-(azepan-1-yl)-N-(6-sulfamoyl-2-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

142) 2-(4,4-difluoroazepan-1-yl)-6-methoxy-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

143) N-(2-methoxypyridin-4-yl)-2-(6-azaspiro[2.5]octan-6-yl)-5-(trifluoromethyl)nicotinamide;

144) 2-(4,4-difluoroazepan-1-yl)-N-(5-sulfamoyl-3-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

145) 2-(azepan-1-yl)-N-(5-sulfamoyl-3-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

146) 2-(4,4-difluoroazepan-1-yl)-N-(2-methoxy-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

147) 2-((3S,5R)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)-N-(2-(methylsulfonyl)pyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

148) 2-[(3R)-4,4-difluoro-3-methyl-1-piperidyl]-N-(2-methylsulfonyl-4-pyridyl)-5-(trifluoro-methyl)-pyridine-3-carboxamide;

149) 2-[(3S)-4,4-difluoro-3-methyl-1-piperidyl]-N-(2-methylsulfonyl-4-pyridyl)-5-(trifluoro-methyl)-pyridine-3-carboxamide;

150) N-(2-cyano-4-pyridyl)-2-[(3S,5R)-4,4-difluoro-3,5-dimethyl-1-piperidyl]-5-(trifluoro-methyl)-pyridine-3-carboxamide;

151) N-(2-methylsulfonyl-4-pyridyl)-2-[(1R,5S)-6,6,7,7-tetrafluoro-3-azabicyclo[3.2.0]heptan-3-yl]-5-(trifluoromethyl)pyridine-3-carboxamide;

152) 2-[(1R,5S)-3-azabicyclo[3.2.0]heptan-3-yl]-N-(2-methylsulfonyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

153) 2-[(1R,5S)-3-azabicyclo[3.2.0]heptan-3-yl]-N-(2-cyano-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

154) (R)—N-(2-cyanopyridin-4-yl)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-5-(trifluoromethyl)-nicotinamide;

155) (S)—N-(2-cyanopyridin-4-yl)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-5-(trifluoromethyl)-nicotinamide;

156) 4-(2-((3S,5R)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)-5-(trifluoromethyl)nicotinamido)-picolinamide;

157) N-(2-carbamoyl-4-pyridyl)-2-[(3S)-4,4-difluoro-3-methyl-1-piperidyl]-5-(trifluoromethyl)-pyridine-3-carboxamide;

158) N-(2-carbamoyl-4-pyridyl)-2-[(3R)-4,4-difluoro-3-methyl-1-piperidyl]-5-(trifluoromethyl)-pyridine-3-carboxamide;

159) 2-(4,4-difluoropiperidin-1-yl)-4-methoxy-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

160) 5-chloro-6-cyclobutyl-2-((2R,6S)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

161) 5-chloro-6-cyclobutyl-2-((2S,6R)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

162) (R)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoro-methyl)nicotinamide;

163) (S)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoro-methyl)nicotinamide;

164) (S)-5-chloro-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoromethyl)nicotinamide;

165) (R)-5-chloro-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoromethyl)nicotinamide;

166) 6-cyclobutyl-2-((3S,5R)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

167) 6-cyclobutyl-2-((2R,6S)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

168) 6-cyclobutyl-2-((2S,6R)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

169) 5-chloro-6-cyclobutyl-2-((3S,5R)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)-N-(2-sulfamoyl-pyridin-4-yl)nicotinamide;

170) 6-chloro-2-(4,4-difluoropiperidin-1-yl)-4-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

171) 2-(4,4-difluoroazepan-1-yl)-5-(difluoromethoxy)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

172) 5-chloro-2-(4,4-difluoroazepan-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

173) 4-(4,4-difluoroazepan-1-yl)-2-methyl-N-(2-sulfamoylpyridin-4-yl)pyrimidine-5-carboxamide;

174) 2-(4,4-difluoroazepan-1-yl)-6-(difluoromethyl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

175) 2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl) nicotinamide;

176) 4-(2-(4,4-difluoropiperidin-1-yl)-5-(trifluoromethyl)nicotinamido)pyridine-2-sulfonic acid;

177) 2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethoxy)nicotinamide 178) 2-(4,4-difluoropiperidin-1-yl)-5-fluoro-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

179) 3-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoromethyl)pyridazine-4-carboxamide;

180) 5-(tert-butyl)-2-(4,4-difluoropiperidin-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)-nicotinamide;

181) 5-cyclopropyl-2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoro-methyl)-nicotinamide;

182) 5-cyclopropyl-2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-6-(trifluoro-methoxy)-nicotinamide;

183) 2-(4,4-difluoropiperidin-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)-5-(2,2,2-trifluoro-ethoxy)-nicotinamide;

184) 2-(4,4-difluoroazepan-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

185) 6-cyclopropyl-2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoro-methyl)nicotinamide;

186) 2-(azepan-1-yl)-N-(5-fluoropyridin-3-yl)-5-(trifluoromethyl)nicotinamide;

187) 2-(azepan-1-yl)-5-chloro-N-(2-methoxy-4-pyridyl)-4,6-dimethyl-pyridine-3-carboxamide;

188) 2-(azepan-1-yl)-5-chloro-4,6-dimethyl-N-(5-sulfamoyl-3-pyridyl)pyridine-3-carboxamide;

189) 5-chloro-2-(4,4-difluoro-1-piperidyl)-4,6-dimethyl-N-(5-sulfamoyl-3-pyridyl)pyridine-3-carboxamide;

190) 2-(6-azaspiro[2.5]octan-6-yl)-5-chloro-4,6-dimethyl-N-(5-sulfamoyl-3-pyridyl)pyridine-3-carboxamide;

191) 5-chloro-4,6-dimethyl-2-(1-piperidyl)-N-(5-sulfamoyl-3-pyridyl)pyridine-3-carboxamide;

192) 2-(4,4-difluoroazepan-1-yl)-6-methoxy-N-(5-sulfamoyl-3-pyridyl)pyridine-3-carboxamide;

193) 2-(azepan-1-yl)-N-(5-cyano-3-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

194) 2-(azepan-1-yl)-N-(5-methoxy-3-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

195) 2-(azepan-1-yl)-N-(5-methyl-3-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

196) 2-(azepan-1-yl)-N-[5-(hydroxymethyl)-3-pyridyl]-5-(trifluoromethyl)pyridine-3-carboxamide;

197) 2-(azepan-1-yl)-N-(2-cyano-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

198) 2-(azepan-1-yl)-N-(2-ethylsulfonyl-4-pyridyl)-5-(trifluoromethyl)pyridine-3-carboxamide;

199) 2-(azepan-1-yl)-N-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-(trifluoromethyl)pyridine-3-carboxamide;

200) 2-(azepan-1-yl)-5-(trifluoromethyl)-N-[5-(trifluoromethyl)-3-pyridyl]pyridine-3-carboxamide;

201) 2-(azepan-1-yl)-5-chloro-4,6-dimethyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

202) 5-chloro-4,6-dimethyl-2-(6-azaspiro[2.5]octan-6-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

203) 4-(2-(azepan-1-yl)-5-(trifluoromethyl)nicotinamido)picolinamide;

204) 5-bromo-2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

205) 2-(4,4-difluoropiperidin-1-yl)-5-phenyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

206) 2-(4,4-difluoropiperidin-1-yl)-5-(piperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

207) 2-(4,4-difluoropiperidin-1-yl)-5-(1H-pyrazol-1-yl)-N-(2-sulfamoylpyridin-4-yl)-nicotinamide;

208) N-(2-oxo-1,2-dihydropyridin-4-yl)-2-(6-azaspiro[2.5]octan-6-yl)-5-(trifluoromethyl)-nicotinamide;

209) 5-chloro-4,6-dimethyl-N-(2-oxo-1,2-dihydropyridin-4-yl)-2-(6-azaspiro[2.5]octan-6-yl)nicotinamide;

210) 2-(4,4-difluoroazepan-1-yl)-N-(2-oxo-1,2-dihydropyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

211) 5-chloro-4,6-dimethyl-N-(2-oxo-1,2-dihydropyridin-4-yl)-2-(piperidin-1-yl)nicotinamide;

212) 2-(azepan-1-yl)-N-(2-oxo-1,2-dihydropyridin-4-yl)-5-(trifluoromethyl)nicotinamide; and

213) 2-(azepan-1-yl)-5-chloro-4,6-dimethyl-N-(2-oxo-1,2-dihydropyridin-4-yl)nicotinamide;

or a pharmaceutically acceptable salt thereof.

19 . The compound according to claim 1 selected from:

1) 5-chloro-2-(4,4-difluorocyclohexyl)-4,6-dimethyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

2) 5-chloro-2-cycloheptyl-4,6-dimethyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide 3) 5-chloro-3-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)pyrazine-2-carboxamide;

4) 5-chloro-4,6-dimethyl-2-(4-methylcyclohexyl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide; and

5) 5-chloro-2-(4,4-difluoroazepan-1-yl)-N,4,6-trimethyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

or a pharmaceutically acceptable salt thereof.

20 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

21 - 25 . (canceled)

26 . A method of treating or preventing a disorder, condition or disease that is responsive to the inhibition of Na v 1.8 channel activity in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

27 . The method of claim 26 wherein the disorder is selected from: pain disorder, a cough disorder, an acute itch disorder or chronic itch disorder.

28 . The method of claim 27 wherein the disorder is a pain disorder.

29 . The method of claim 28 wherein the pain disorder is selected from: acute pain, inflammatory pain, or neuropathic pain.

30 . The compound according to claim 1 selected from:

1) (S)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

2) (R)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

3) 2-(4,4-difluoroazepan-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)-nicotinamide;

4) 2-(4,4-difluoroazepan-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide;

5) 5-chloro-6-cyclobutyl-2-((2R,6S)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

6) 5-chloro-6-cyclobutyl-2-((2S,6R)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

7) 5-chloro-2-(4,4-difluoroazepan-1-yl)-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

8) 2-(4,4-difluoroazepan-1-yl)-6-(difluoromethyl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

9) 2-(4,4-difluoropiperidin-1-yl)-5-fluoro-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

10) 2-(4,4-difluoropiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl) nicotinamide;

11) 5-chloro-6-cyclobutyl-2-((3S,5R)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)nicotinamide;

12) 4-(2-(4,4-difluoroazepan-1-yl)-5-(trifluoromethyl)nicotinamido)picolinamide;

13) 5-chloro-6-cyclopropyl-2-(4,4-difluoroazepan-1-yl)-N-(2-oxo-1,2-dihydro-pyridin-4-yl)nicotinamide; and

14) 2-(4,4-difluoroazepan-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)-nicotinamide;

or a pharmaceutically acceptable salt thereof.

31 . The compound according to claim 1 which is (S)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide; or a pharmaceutically acceptable salt thereof.

32 . The compound according to claim 1 which is (R)-2-(4,4-difluoro-3-methylpiperidin-1-yl)-N-(2-sulfamoylpyridin-4-yl)-5-(trifluoromethyl)nicotinamide; or a pharmaceutically acceptable salt thereof.

33 . The compound according to claim 1 which is 5-chloro-6-cyclobutyl-2-((2R,6S)-2-methyl-6-(trifluoromethyl)morpholino)-N-(2-sulfamoylpyridin-4-yl)-nicotinamide; or a pharmaceutically acceptable salt thereof.

34 . The compound according to claim 1 which is 2-(4,4-difluoro-piperidin-1-yl)-5-fluoro-6-methyl-N-(2-sulfamoylpyridin-4-yl)nicotinamide; or a pharmaceutically acceptable salt thereof.

35 . The compound according to claim 1 which is 5-chloro-6-cyclopropyl-2-(4,4-difluoroazepan-1-yl)-N-(2-oxo-1,2-dihydropyridin-4-yl)nicotinamide; or a pharmaceutically acceptable salt thereof.